A universal recombinant adenovirus type 5 vector-based COVID-19 vaccine

Front Immunol. 2024 Apr 30:15:1374486. doi: 10.3389/fimmu.2024.1374486. eCollection 2024.

Abstract

A universal recombinant adenovirus type-5 (Ad5) vaccine against COVID19 (Ad-US) was constructed, and immunogenicity and broad-spectrum of Ad5-US were evaluated with both intranasal and intramuscular immunization routes. The humoral immune response of Ad5-US in serum and bronchoalveolar lavage fluid were evaluated by the enzyme-linked immunosorbent assay (ELISA), recombinant vesicular stomatitis virus based pseudovirus neutralization assay, and angiotensin-converting enzyme-2 (ACE2) -binding inhibition assay. The cellular immune response and Th1/Th2 biased immune response of Ad5-US were evaluated by the IFN-γ ELISpot assay, intracellular cytokine staining, and Meso Scale Discovery (MSD) profiling of Th1/Th2 cytokines. Intramuscular priming followed by an intranasal booster with Ad5-US elicited the broad-spectrum and high levels of IgG, IgA, pseudovirus neutralizing antibody (PNAb), and Th1-skewing of the T-cell response. Overall, the adenovirus type-5 vectored universal SARS-CoV-2 vaccine Ad5-US was successfully constructed, and Ad5-US was highly immunogenic and broad spectrum. Intramuscular priming followed by an intranasal booster with Ad5-US induced the high and broad spectrum systemic immune responses and local mucosal immune responses.

Keywords: SARS-COV-2 variants; adenovirus type-5; broad-spectrum; universal COVID-19 vaccine; vaccination route.

MeSH terms

  • Adenoviridae / genetics
  • Adenoviridae / immunology
  • Administration, Intranasal
  • Animals
  • Antibodies, Neutralizing* / blood
  • Antibodies, Neutralizing* / immunology
  • Antibodies, Viral* / blood
  • Antibodies, Viral* / immunology
  • COVID-19 Vaccines* / administration & dosage
  • COVID-19 Vaccines* / immunology
  • COVID-19* / immunology
  • COVID-19* / prevention & control
  • Cytokines / metabolism
  • Female
  • Genetic Vectors*
  • Humans
  • Immunity, Cellular
  • Immunity, Humoral
  • Injections, Intramuscular
  • Mice
  • Mice, Inbred BALB C
  • SARS-CoV-2* / genetics
  • SARS-CoV-2* / immunology
  • Vaccines, Synthetic / administration & dosage
  • Vaccines, Synthetic / immunology

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was supported by National Key Research and Development Program of China (No.2021YFC2302404).